Crohn's disease (CD) and Ulcerative Colitis (UC) are Inflammatory Bowel Diseases (IBDs) of unknown etiology. Although the exact pathogenesis is poorly understood, there is evidence that it involves interactions between the immune system, genetic susceptibility and the environment. One of the complications of longstanding ulcerative colitis (UC) is the development of cancer. Understanding why some patients with long standing colitis develop dysplasia while others do not is an important question that remains unanswered. The central hypothesis of this proposal is that NK1R- and EGFR-signaling pathways play critical roles in the development of colitis-associated dysplasia. The specific aims of the proposed plan are to: 1) to investigate the role of NK1 receptors in our model of colitis-associated dysplasia versus chronic inflammation;2) to analyze the role of EGFR in chronic inflammation and colitis-associated dysplasia;3) evaluate the effects of EGFR and COX-2 inhibitors on the occurrence of colitis-associated dysplasia. These studies will help to understand the involvement of the SP-NK1R-EGFR signaling pathways in UC-associated CRC and how inhibitors could eventually be used as a potential therapy in patients with long standing colitis.